Post-exposure HIV prophylaxis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

adults or adolescents ≥13 years: nonpregnant

with normal renal function

1st line – three-drug antiretroviral regimen

Back

1st line –

three-drug antiretroviral regimen

Post-exposure prophylaxis (PEP) should be started within 72 hours of exposure.[49] Treatment duration is 28 days.

The Centers for Disease Control and Prevention (CDC) and the UK British Association for Sexual Health and HIV (BASHH) both recommend a 3-drug regimen.[3][4] The World Health Organization (WHO) states that a 2-drug regimen is effective, but a 3-drug regimen is preferred.[58]

The CDC recommends the following PEP regimens in adults and adolescents with normal renal function: emtricitabine/tenofovir disoproxil plus raltegravir or dolutegravir; or emtricitabine/tenofovir disoproxil plus darunavir/ritonavir as an alternative.[4]

The BASHH recommends the following PEP regimens in adults and adolescents with normal renal function: emtricitabine/tenofovir disoproxil plus raltegravir; or emtricitabine/tenofovir disoproxil plus elvitegravir/cobicistat as an alternative.[3]

The WHO recommends the following PEP regimens in adults and adolescents with normal renal function: tenofovir disoproxil plus emtricitabine or lamivudine as the preferred backbone, plus dolutegravir as the preferred third drug. Alternative third drugs include atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir, or raltegravir.[58]

Consult your local guidelines for specific drug regimens as they may vary.

Contraindications, drug-drug interactions, adverse effects, adherence, viral resistance, and toxicity are issues to consider when prescribing these regimens. An alternative regimen may need to be prescribed in some patients. Consult an HIV specialist for further guidance.

Consult a specialist or your local drug formulary for guidance on doses. Some drug combinations may be available as co-formulations.

Primary options

CDC regimen

emtricitabine/tenofovir disoproxil

-- AND --

dolutegravir

or

raltegravir

OR

BASHH regimen

emtricitabine/tenofovir disoproxil

and

raltegravir

OR

WHO regimen

emtricitabine/tenofovir disoproxil

or

lamivudine/tenofovir disoproxil

-- AND --

dolutegravir

Secondary options

CDC regimen

emtricitabine/tenofovir disoproxil

and

darunavir

and

ritonavir

OR

BASHH regimen

emtricitabine/tenofovir disoproxil

and

elvitegravir

and

cobicistat

OR

WHO regimen

emtricitabine/tenofovir disoproxil

or

lamivudine/tenofovir disoproxil

-- AND --

atazanavir

or

darunavir

or

lopinavir/ritonavir

or

raltegravir

Plus – counseling and support

Back

Plus –

counseling and support

Treatment recommended for ALL patients in selected patient group

Counseling is an important step in the management of post-exposure prophylaxis (PEP). The purpose, rationale, and efficacy of PEP should be explained so that the patient can make an informed decision whether to start the regimen.

The importance of completing the full 28-day regimen should be stressed. Adherence to a full 28-day course of PEP has been shown to be poor in multiple studies.[61] Adherence counseling may help with this, especially if psychosocial stressors affecting adherence can be addressed.[62]

Medication should be started as soon as possible and taken each day according to the schedule that best fits the patient’s daily routine, in order to encourage adherence. People should be warned about adverse effects (e.g., fatigue, headache, rash, nausea, and diarrhea) and toxicities (e.g., liver dysfunction and anemia).

Counseling should address risk reduction strategies for the future and the importance of safe sex, especially in the HIV-testing window period. This is particularly relevant for patients who have had multiple sexual exposures to HIV and may offer an opportunity to discuss the potential for high-risk individuals to transition to pre-exposure prophylaxis (PrEP) when PEP is completed.[3][42]

Patients should be warned about potential drug-drug interactions with the PEP regimen, including over-the-counter medications (including herbal or alternative medicines) as well as prescribed medications.

HIV pre-test discussion should be carried out prior to the baseline HIV test, and investigations and importance of follow-up made clear. Patients should also be counseled regarding the symptoms of seroconversion. Flu-like illness with fever, sore throat, rash, or diarrhea may occur, but more severe symptoms have also been documented. This may occur up to 12 weeks after exposure.[55]

People who have been either occupationally or sexually exposed to HIV may need close psychological support (this may apply especially to those who have been sexually assaulted). Patients who have been exposed to HIV through rape or other sexual assaults should be offered a referral to a rape crisis group and should receive support from social workers and case managers, including discussion of any ongoing domestic violence.

with renal impairment

1st line – three-drug antiretroviral regimen with alternative two-drug backbone

Back

1st line –

three-drug antiretroviral regimen with alternative two-drug backbone

Post-exposure prophylaxis (PEP) should be started within 72 hours of exposure.[49] Treatment duration is 28 days.

The Centers for Disease Control and Prevention (CDC) and the UK British Association for Sexual Health and HIV (BASHH) both recommend a 3-drug regimen.[3][4]

The CDC recommends the following PEP regimens in adults and adolescents with renal impairment: zidovudine plus lamivudine plus raltegravir or dolutegravir; or zidovudine plus lamivudine plus darunavir/ritonavir as an alternative.[4]

The BASHH recommends the following PEP regimens in adults and adolescents with renal impairment: emtricitabine/tenofovir alafenamide plus raltegravir (reduced dose) or dolutegravir; or emtricitabine/tenofovir alafenamide plus darunavir/ritonavir or atazanavir/ritonavir; or emtricitabine/tenofovir alafenamide plus elvitegravir/cobicistat as an alternative.[3]

Consult your local guidelines for specific drug regimens as they may vary.

Tenofovir is available as tenofovir disoproxil or the oral prodrug tenofovir alafenamide. The BASHH recommends tenofovir alafenamide in preference to tenofovir disoproxil in patients with renal impairment as the prodrug is associated with less renal toxicity.[3] As the CDC guidelines are older, they do not currently recommend tenofovir alafenamide as an option in these patients.

For patients with severe renal impairment (estimated glomerular filtration rate <30 mL/minute), expert advice should be sought from a specialist.[3]

Contraindications, drug-drug interactions, adverse effects, adherence, viral resistance, and toxicity are issues to consider when prescribing these regimens. An alternative regimen may need to be prescribed in some patients. Consult an HIV specialist for further guidance.

Consult a specialist or your local drug formulary for guidance on doses. Some drug combinations may be available as co-formulations.

Primary options

CDC regimen

lamivudine/zidovudine

-- AND --

dolutegravir

or

raltegravir

OR

BASHH regimen

emtricitabine/tenofovir alafenamide

-- AND --

raltegravir

or

dolutegravir

OR

BASHH regimen

emtricitabine/tenofovir alafenamide

-- AND --

darunavir

or

atazanavir

Secondary options

CDC regimen

lamivudine/zidovudine

and

darunavir

and

ritonavir

OR

BASHH regimen

emtricitabine/tenofovir alafenamide

and

elvitegravir

and

cobicistat

Plus – counseling and support

Back

Plus –

counseling and support

Treatment recommended for ALL patients in selected patient group

Counseling is an important step in the management of post-exposure prophylaxis (PEP). The purpose, rationale, and efficacy of PEP should be explained so that the patient can make an informed decision whether to start the regimen.

The importance of completing the full 28-day regimen should be stressed. Adherence to a full 28-day course of PEP has been shown to be poor in multiple studies.[61] Adherence counseling may help with this, especially if psychosocial stressors affecting adherence can be addressed.[62]

Medication should be started as soon as possible and taken each day according to the schedule that best fits the patient’s daily routine, in order to encourage adherence. People should be warned about adverse effects (e.g., fatigue, headache, rash, nausea, and diarrhea) and toxicities (e.g., liver dysfunction and anemia).

Counseling should address risk reduction strategies for the future and the importance of safe sex, especially in the HIV-testing window period. This is particularly relevant for patients who have had multiple sexual exposures to HIV and may offer an opportunity to discuss the potential for high-risk individuals to transition to pre-exposure prophylaxis (PrEP) when PEP is completed.[3][42]

Patients should be warned about potential drug-drug interactions with the PEP regimen, including over-the-counter medications (including herbal or alternative medicines) as well as prescribed medications.

HIV pre-test discussion should be carried out prior to the baseline HIV test, and investigations and importance of follow-up made clear. Patients should also be counseled regarding the symptoms of seroconversion. Flu-like illness with fever, sore throat, rash, or diarrhea may occur, but more severe symptoms have also been documented. This may occur up to 12 weeks after exposure.[55]

People who have been either occupationally or sexually exposed to HIV may need close psychological support (this may apply especially to those who have been sexually assaulted). Patients who have been exposed to HIV through rape or other sexual assaults should be offered a referral to a rape crisis group and should receive support from social workers and case managers, including discussion of any ongoing domestic violence.

pregnant or breastfeeding

1st line – specialist referral

Back

1st line –

specialist referral

Pregnancy is not a contraindication for post-exposure prophylaxis (PEP), and the regimens used in nonpregnant individuals may be used in pregnant women. However, an appropriate regimen should be selected under specialist consultation. All women of childbearing potential should have a pregnancy test before starting PEP.

There was previously a concern that dolutegravir may increase the risk of neural tube defects in infants born to women who conceived while taking the drug, based on an interim analysis of data from a surveillance study in Botswana. However, more recent studies have found the risk to be lower than initially thought, and the most recent data from the Botswana study indicate that the prevalence of neural tube defects was not significantly different than in those receiving other antiretrovirals. US guidelines therefore consider the use of dolutegravir to be safe throughout pregnancy.[49]

Despite this, the UK British Association for Sexual Health and HIV guidelines recommend avoiding dolutegravir as the third drug in women at risk of pregnancy or known to be within the first 6 weeks of pregnancy who cannot use a first-line PEP regimen for any reason. However, it may be used in pregnant women who are more than 6 weeks pregnant.[3] The World Health Organization recommends that the use of dolutegravir is conditional upon access to consistent and reliable contraception.[58] However, it should be noted that both of these guidelines were published before the current US guidelines.

Breastfeeding is not a contraindication for PEP, but women should be counseled on the risk of infant exposure to antiretrovirals via breastmilk.[3]

children

1st line – specialist referral

Back

1st line –

specialist referral

There are few data regarding the administration of post-exposure prophylaxis (PEP) to children. The choice of antiretroviral regimen depends on the child’s age. The dosing of antiretrovirals is weight-based for some regimens. Some medications come in liquid formulations that can be easier for children to take. It is advisable to consult with a pediatric HIV specialist if considering PEP in children. Specific details on PEP regimens in children are beyond the scope of this topic.

Children and adolescents who have been sexually assaulted should ideally be managed in the emergency department or other setting where age-appropriate resources are available to address the multiple medical, psychosocial, and legal issues related to such an offense.

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